Many, perhaps most, types of malignant cells display antigens which are recognized as foreign by our immune surveillance mechanism. Interestingly, many antigens detected on tumor cells are also found on specific cell types in embryos. The exact significance of this correlation is not yet understood. We are exploring this relationship in our research program. During the first funding period of this grant (13 months) we have: 1) established a program of research on a new type of highly antigenic, tumor-specific transplantation antigens; 2) shown that maternal immunity against these tumors induces specific embryologic defects; 3) developed new immunological reagents and utilized them in studies of these tumor cell surfaces by fluorescent light microscopy and scanning electron microscopy; 4) developed other microspherical immunoreagents for use in cell separation and isolation of cell surface antigens. We propose to continue these studies. Several approaches will be taken in an effort to characterize the tumor antigens and compare them with antigens displayed on normal cells at various stages of development. We plan to determine 1) the location and the nature of cells affected when fetal developmental anomalies are induced by immunization of parent female mice with a series of tumors, each displaying different antigen; 2) whether there is an order or pattern of cross-reactivity of different tumor lines with cells found in specific regions of developing embryos; 3) the molecular properties of the tumor antigens and how they relate to each other and to other known cell surface antigens. We also plan to initiate an experimental protocol designed to investigate the biological function of the molecules known as cell surface antigens. We believe that data obtained will help to explain the genetic, molecular and cellular basis for the appearance of such antigens on cell surfaces and may provide new insignts into the role of the cell surface in normal embryogenesis and in abnormal cell growth.